The Pharmacokinetics of Ketorolac Tromethamine Administered Intranasally (IN) for Postoperative Pain in Children Aged 12 Through 17 Years

A Study of the Pharmacokinetics of Ketorolac Tromethamine Administered Intranasally (IN) for Postoperative Pain in Children Aged 12 Through 17 Years

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01363076

Enrollment

Registered

2011-06-01

Start date

2007-06-30

Completion date

2008-05-31

Last updated

2017-03-16

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Postoperative Pain

Brief summary

This was an open-label PK study in pediatric subjects who had undergone general surgery. Each subject's study participation consisted of a screening visit, a single-dose treatment with intranasal ketorolac (IN) tromethamine, and a follow-up visit. Following surgery, subjects received IN ketorolac 15 mg (weight \< 50 kg) or 30 mg (weight \> or = 50 kg) when pain relief was indicated. For pain not relieved by the study drug, the subjects had access to an opioid analgesic administered by patient-controlled analgesia (PCA). Blood samples for pharmacokinetic analysis were obtained at specified time points following the dose of ketorolac.

Interventions

DRUGKetorolac Tromethamine

Single IN dose of 15 mg ketorolac tromethamine for subjects weighing \<50 kg.

Study design

Allocation

NON_RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

12 Years to 17 Years

Healthy volunteers

Inclusion criteria

* Children aged 12 through 17 years * Body weight \> or = 30 kg and \< or = 100 kg * Female subjects of childbearing potential must have a negative serum or urine pregnancy test result prior to entry into the study * A legal representative able to provide written informed consent * Willing and able to comply with all testing and requirements defined in the protocol * Willing and able to complete the posttreatment visit

Exclusion criteria

* Allergy or sensitivity to ketorolac or ethylene diamine tetraacetic acid (EDTA) * Allergic reaction to aspirin or other NSAIDs * Had an upper respiratory tract infection or other respiratory tract condition (eg, active allergic rhinitis) that could interfere with the absorption of the nasal spray or with the assessment of AEs * Use of any IN product within 24 hours prior to study entry * Clinically significant abnormality on screening laboratory tests * History of cocaine use resulting in nasal mucosal damage * History of peptic ulcer disease or gastrointestinal bleeding * Had advanced renal impairment or a risk for renal failure due to volume depletion * A history of any other clinically significant medical problem, which in the opinion of the investigator would interfere with study participation * Participation within 30 days of study entry or within 5 times the half-life, whichever is longer, in another investigational drug study * Allergy or significant reaction to opioids * Was pregnant or breastfeeding * Previously participated in this study * The surgical procedure involved head, neck, oral, or nasal surgery

Design outcomes

Primary

Measure	Time frame	Description
Cmax (the Maximum Observed Plasma Concentration)	All PK parameters were assessed using blood samples collected 15 minutes prior to the dose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, and 24 hours after the dose	Pharmacokinetic analysis by standard model independent methods was performed by a pharmacokineticist using WinNonlin Professional. Actual blood sampling times for ketorolac assay were converted to a time from dosing (elapsed time). Elapsed times were listed by subject for each dose level, together with the individual plasma concentrations of ketorolac.
Tmax (The Time to Maximum Observed Plasma Concentration; ie. The Time at Which Cmax Occured)	All PK parameters were assessed using blood samples collected 15 minutes prior to the dose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, and 24 hours after the dose	Pharmacokinetic analysis by standard model independent methods was performed by a pharmacokineticist using WinNonlin Pro. Actual blood sampling times for ketorolac assay were converted to a time from dosing (elapsed time). Elapsed times were listed by subject for each dose level, together with the individual plasma concentrations of ketorolac. Individual plasma ketorolac concentrations were summarized by dose level for the PK population at each sampling time using n, arithmetic mean, SD, CV(%), geometric mean, 95% confidence intervals (CI) for the arithmetic mean, median, minimum, and maximum.
AUClast (the Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to the Last Quantifiable Timepoint Post-dose)	All PK parameters were assessed using blood samples collected 15 minutes prior to the dose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, and 24 hours after the dose	Pharmacokinetic analysis by standard model independent methods was performed by a pharmacokineticist using WinNonlin Professional. Actual blood sampling times for ketorolac assay were converted to a time from dosing (elapsed time). Elapsed times were listed by subject for each dose level, together with the individual plasma concentrations of ketorolac.
AUCinf (the AUC Time From Zero to Infinity, Where Possible)	All PK parameters were assessed using blood samples collected 15 minutes prior to the dose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, and 24 hours after the dose	Pharmacokinetic analysis by standard model independent methods was performed by a pharmacokineticist using WinNonlin Pro. Actual blood sampling times for ketorolac assay were converted to a time from dosing (elapsed time). Elapsed times were listed by subject for each dose level, together with the individual plasma concentrations of ketorolac. AUCinf calculated as: AUCinf = AUC(0-24) + (concentration at 24 hr/elimination constant).
AUC 0-24 (the AUC From Time Zero to 24 Hours Post-dose	All PK parameters were assessed using blood samples collected 15 minutes prior to the dose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, and 24 hours after the dose	Pharmacokinetic analysis by standard model independent methods was performed by a pharmacokineticist using WinNonlin Professional. Actual blood sampling times for ketorolac assay were converted to a time from dosing (elapsed time). Elapsed times were listed by subject for each dose level, together with the individual plasma concentrations of ketorolac.
t1/2 (the Terminal Half-life, Where Possible)	All PK parameters were assessed using blood samples collected 15 minutes prior to the dose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, and 24 hours after the dose	Pharmacokinetic analysis by standard model independent methods was performed by a pharmacokineticist using WinNonlin Professional. Actual blood sampling times for ketorolac assay were converted to a time from dosing (elapsed time). Elapsed times were listed by subject for each dose level, together with the individual plasma concentrations of ketorolac.
MRT (Mean Residence Time)	All PK parameters were assessed using blood samples collected 15 minutes prior to the dose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, and 24 hours after the dose	Pharmacokinetic analysis by standard model independent methods was performed by a pharmacokineticist using WinNonlin Professional. Actual blood sampling times for ketorolac assay were converted to a time from dosing (elapsed time). Elapsed times were listed by subject for each dose level, together with the individual plasma concentrations of ketorolac.

Countries

United States

Participant flow

Recruitment details

Recruitment Period: June 2007 - January 2008; Location: Stanford University Medical Center

Pre-assignment details

Screening procedure consisting of an interview and the following assessments: demographics, medical history, physical examination, concomitant medications within last 30 days, vital signs, clinical laboratory tests, pregnancy test (female subjects).

Participants by arm

Arm	Count
Ketorolac Tromethamine (15 mg) Single intranasal (IN) dose of 15 mg ketorolac tromethamine for subjects weighing \<50 kg.	7
Ketorolac Tromethamine (30 mg) Single intranasal (IN) dose of 30 mg ketorolac tromethamine for subjects weighing ≥50 kg.	13
Total	20

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Withdrawal by Subject	0	1

Baseline characteristics

Characteristic	Ketorolac Tromethamine (30 mg)	Ketorolac Tromethamine (15 mg)	Total
Age, Categorical <=18 years	13 Participants	7 Participants	20 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	0 Participants	0 Participants	0 Participants
Age, Continuous	15.4 years STANDARD_DEVIATION 1.6	14.1 years STANDARD_DEVIATION 0.7	15.0 years STANDARD_DEVIATION 1.5
Region of Enrollment United States	13 participants	7 participants	20 participants
Sex: Female, Male Female	4 Participants	3 Participants	7 Participants
Sex: Female, Male Male	9 Participants	4 Participants	13 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	3 / 7	8 / 13
serious Total, serious adverse events	0 / 7	1 / 13

Outcome results

Primary

AUC 0-24 (the AUC From Time Zero to 24 Hours Post-dose

Pharmacokinetic analysis by standard model independent methods was performed by a pharmacokineticist using WinNonlin Professional. Actual blood sampling times for ketorolac assay were converted to a time from dosing (elapsed time). Elapsed times were listed by subject for each dose level, together with the individual plasma concentrations of ketorolac.